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Gene Review

RTL1  -  retrotransposon-like 1

Homo sapiens

Synonyms: MAR1, MART1, Mammalian retrotransposon derived protein 1, Mar1, PEG11, ...
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Disease relevance of RTL1

  • Here we analyzed the responses to synthetic peptides of HLA-A2.1-restricted CTL clones specific for melanoma antigens MART-1 and NA17-A [1].
  • Partial protection against a challenge with NFSA(MART1) could be achieved with i.m. injections of a MART-1 expression plasmid or with systemic administration of an adenovirus vector expressing MART-1 [2].
  • Tumor lesions in lymphoid and nonlymphoid tissues (metastatic lymph nodes and soft tissue/visceral metastases, respectively) were collected from stage III/IV melanoma patients and investigated for the presence and function of CD8 T cells specific for the tumor differentiation antigen Melan-A/MART-1 [3].
  • A poorly immunogenic murine fibrosarcoma line (NFSA) was stably transfected with the MART-1 gene [2].
  • We have investigated the possible usefulness of recombinant canarypox virus (ALVAC) encoding the melanoma-associated Ag, Melan-A/MART-1 (MART-1), in cancer immunotherapy, using a dendritic cell (DC)-based approach [4].

High impact information on RTL1

  • Here we show that the imprinted mouse distal chromosome 12 locus encodes two miRNA genes expressed from the maternally inherited chromosome and antisense to a retrotransposon-like gene (Rtl1) expressed only from the paternal allele [5].
  • Using fluorescent HLA-A*0201 tetramers containing the immunodominant Melan-A/MART-1 (Melan-A) tumor-associated antigen (Ag), we previously observed that metastatic lymph nodes of melanoma patients contain high numbers of Ag-experienced Melan-A-specific cytolytic T lymphocytes (CTLs) [6].
  • High frequencies of naive Melan-A/MART-1-specific CD8(+) T cells in a large proportion of human histocompatibility leukocyte antigen (HLA)-A2 individuals [6].
  • Analysis of a melanocyte-specific phenotype marker (MART-1) and a neuronal marker (Tuj1) revealed a subpopulation of melanoma cells that invade the chick periphery and express MART-1 and Tuj1 [7].
  • The MCS1a sequence was found to comprise a portion of the long terminal repeats of a retrotransposon-like repeated element, termed CentA [8].

Chemical compound and disease context of RTL1


Biological context of RTL1

  • Two of the autosomal gene members, Peg10 and Rtl1, are known to be imprinted, being expressed from the paternally inherited chromosome homologue [12].
  • Furthermore, the methylation status of Rtl1 was assayed throughout development and was found to resemble that of actively, silenced repetitive elements rather than imprinted sequences [12].
  • The cloning and expression of functional TCR genes which are capable of specifically recognizing MART-1 antigen provides reagents which could be used for the study of the mechanisms of T-cell/tumor antigen interactions and creates immortalized reagents which can facilitate studies requiring detection of the MART-1 antigen [13].
  • One consistent feature of infection by ALVAC is that these viruses induce apoptosis, and we show cross-presentation of Ag when uninfected DC are cocultured with ALVAC MART-1-infected DC [4].
  • Significantly, this Ag silencing is reversible, as removal of factor-containing supernatants from Melan-A/MART-1-expressing cells results in up-regulation of the promoter for the gene encoding this Ag, and renewed expression of the protein [14].

Anatomical context of RTL1

  • Recognition of HLA-A2+ melanoma cell lines by the Jurkat clone 5 TCR+ cells, however, did not occur without the addition of exogenous MART-1 peptide [13].
  • Generation of CD8+ and CD4+ T-cell response to dendritic cells genetically engineered to express the MART-1/Melan-A gene [15].
  • Among the immunomodulators, the T-cell antigen MART-1 and the protease inhibitor alpha2-macroglobulin were detected in the melanocyte cell line but not in the tumor cells [16].
  • T-cell receptor repertoire in matched MART-1 peptide-stimulated peripheral blood lymphocytes and tumor-infiltrating lymphocytes [17].
  • Unexpectedly, however, whereas primed Melan-A/MART-1-specific CD8 T cells that circulate in the blood display robust inflammatory and cytotoxic functions, those that reside in tumor lesions (particularly in metastatic lymph nodes) are functionally tolerant [3].

Associations of RTL1 with chemical compounds

  • Intron 9 carries a retrotransposon-like element, Tms1, which might be responsible for downstream deletion events in which a heptanucleotide, ATTAGCT, might have been involved [18].
  • Heart-of-palm (Euterpe edulis Mart.) is a wild palm with a wide distribution throughout the Atlantic Rainforest [19].
  • In this study we demonstrate transgene expression, including expression of the MART-1 gene, in DC transfected with plasmid DNA and cationic liposome complexes [20].
  • Grossamide, and N-TRANS-caffeoyltyramine, were isolated for the first time from the seeds of ANNONA CRASSIFLORA Mart, and in the Annonaceae family [21].
  • Modification of the parental immunodominant Melan-A/MART-1 peptide (MART-1(26-35)) by replacing the alanine with leucine (A27L) enhances its immunogenicity [22].

Other interactions of RTL1


Analytical, diagnostic and therapeutic context of RTL1

  • A superagonist variant of peptide MART1/Melan A27-35 elicits anti-melanoma CD8+ T cells with enhanced functional characteristics: implication for more effective immunotherapy [25].
  • Here, we show that autologous DCs from both HLA-A2-positive melanoma patients and normal healthy individuals that are transduced with an adenoviral vector containing the MART-1 antigen are capable of inducing both MART-1-specific CD8+ and CD4+ T cells in in vitro coculture [15].
  • Replication-deficient recombinant adenovirus (Ad) encoding human gp100 or MART-1 melanoma Ag was used to transduce human dendritic cells (DC) ex vivo as a model system for cancer vaccine therapy [26].
  • Clone DMF5, from a TIL infusion that mediated tumor regression clinically, showed the highest avidity against MART-1 expressing tumors in vitro, both endogenously in the TIL clone, and after RNA electroporation into donor T cells [27].
  • To study the relationship between TCR affinity and cellular avidity, with the intent of identifying optimal TCR for gene therapy, we derived 24 MART-1:27-35 (MART-1) melanoma Ag-reactive tumor-infiltrating lymphocyte (TIL) clones from the tumors of five patients [27].


  1. Suboptimal activation of melanoma infiltrating lymphocytes (TIL) due to low avidity of TCR/MHC-tumor peptide interactions. Gervois, N., Guilloux, Y., Diez, E., Jotereau, F. J. Exp. Med. (1996) [Pubmed]
  2. Genetic immunization for the melanoma antigen MART-1/Melan-A using recombinant adenovirus-transduced murine dendritic cells. Ribas, A., Butterfield, L.H., McBride, W.H., Jilani, S.M., Bui, L.A., Vollmer, C.M., Lau, R., Dissette, V.B., Hu, B., Chen, A.Y., Glaspy, J.A., Economou, J.S. Cancer Res. (1997) [Pubmed]
  3. Effector function of human tumor-specific CD8 T cells in melanoma lesions: a state of local functional tolerance. Zippelius, A., Batard, P., Rubio-Godoy, V., Bioley, G., Liénard, D., Lejeune, F., Rimoldi, D., Guillaume, P., Meidenbauer, N., Mackensen, A., Rufer, N., Lubenow, N., Speiser, D., Cerottini, J.C., Romero, P., Pittet, M.J. Cancer Res. (2004) [Pubmed]
  4. Cross-presentation by dendritic cells of tumor antigen expressed in apoptotic recombinant canarypox virus-infected dendritic cells. Motta, I., André, F., Lim, A., Tartaglia, J., Cox, W.I., Zitvogel, L., Angevin, E., Kourilsky, P. J. Immunol. (2001) [Pubmed]
  5. Imprinted microRNA genes transcribed antisense to a reciprocally imprinted retrotransposon-like gene. Seitz, H., Youngson, N., Lin, S.P., Dalbert, S., Paulsen, M., Bachellerie, J.P., Ferguson-Smith, A.C., Cavaillé, J. Nat. Genet. (2003) [Pubmed]
  6. High frequencies of naive Melan-A/MART-1-specific CD8(+) T cells in a large proportion of human histocompatibility leukocyte antigen (HLA)-A2 individuals. Pittet, M.J., Valmori, D., Dunbar, P.R., Speiser, D.E., Liénard, D., Lejeune, F., Fleischhauer, K., Cerundolo, V., Cerottini, J.C., Romero, P. J. Exp. Med. (1999) [Pubmed]
  7. Reprogramming metastatic melanoma cells to assume a neural crest cell-like phenotype in an embryonic microenvironment. Kulesa, P.M., Kasemeier-Kulesa, J.C., Teddy, J.M., Margaryan, N.V., Seftor, E.A., Seftor, R.E., Hendrix, M.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. Chromosome-specific molecular organization of maize (Zea mays L.) centromeric regions. Ananiev, E.V., Phillips, R.L., Rines, H.W. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  9. Binding and presentation of peptides derived from melanoma antigens MART-1 and glycoprotein-100 by HLA-A2 subtypes. Implications for peptide-based immunotherapy. Rivoltini, L., Loftus, D.J., Barracchini, K., Arienti, F., Mazzocchi, A., Biddison, W.E., Salgaller, M.L., Appella, E., Parmiani, G., Marincola, F.M. J. Immunol. (1996) [Pubmed]
  10. Vitamin A activity of buriti (Mauritia vinifera Mart) and its effectiveness in the treatment and prevention of xerophthalmia. Mariath, J.G., Lima, M.C., Santos, L.M. Am. J. Clin. Nutr. (1989) [Pubmed]
  11. Melan A/MART-1 immunoreactivity in formalin-fixed paraffin-embedded primary and metastatic melanoma: frequency and distribution. Hofbauer, G.F., Kamarashev, J., Geertsen, R., Böni, R., Dummer, R. Melanoma Res. (1998) [Pubmed]
  12. A small family of sushi-class retrotransposon-derived genes in mammals and their relation to genomic imprinting. Youngson, N.A., Kocialkowski, S., Peel, N., Ferguson-Smith, A.C. J. Mol. Evol. (2005) [Pubmed]
  13. Characterization of the functional specificity of a cloned T-cell receptor heterodimer recognizing the MART-1 melanoma antigen. Cole, D.J., Weil, D.P., Shilyansky, J., Custer, M., Kawakami, Y., Rosenberg, S.A., Nishimura, M.I. Cancer Res. (1995) [Pubmed]
  14. A novel autocrine pathway of tumor escape from immune recognition: melanoma cell lines produce a soluble protein that diminishes expression of the gene encoding the melanocyte lineage melan-A/MART-1 antigen through down-modulation of its promoter. Kurnick, J.T., Ramirez-Montagut, T., Boyle, L.A., Andrews, D.M., Pandolfi, F., Durda, P.J., Butera, D., Dunn, I.S., Benson, E.M., Gobin, S.J., van den Elsen, P.J. J. Immunol. (2001) [Pubmed]
  15. Generation of CD8+ and CD4+ T-cell response to dendritic cells genetically engineered to express the MART-1/Melan-A gene. Pérez-Díez, A., Butterfield, L.H., Li, L., Chakraborty, N.G., Economou, J.S., Mukherji, B. Cancer Res. (1998) [Pubmed]
  16. Identification of differentially expressed messenger RNAs in human melanocytes and melanoma cells. Simon, H.G., Risse, B., Jost, M., Oppenheimer, S., Kari, C., Rodeck, U. Cancer Res. (1996) [Pubmed]
  17. T-cell receptor repertoire in matched MART-1 peptide-stimulated peripheral blood lymphocytes and tumor-infiltrating lymphocytes. Cole, D.J., Wilson, M.C., Rivoltini, L., Custer, M., Nishimura, M.I. Cancer Res. (1997) [Pubmed]
  18. The nucleotide sequence of a nodule-specific gene, Nms-25 of Medicago sativa: its primary evolution via exon-shuffling and retrotransposon-mediated DNA rearrangements. Végh, Z., Vincze, E., Kadirov, R., Tóth, G., Kiss, G.B. Plant Mol. Biol. (1990) [Pubmed]
  19. Genetic differentiation of Euterpe edulis Mart. populations estimated by AFLP analysis. Cardoso, S.R., Eloy, N.B., Provan, J., Cardoso, M.A., Ferreira, P.C. Mol. Ecol. (2000) [Pubmed]
  20. Transgene expression in dendritic cells to induce antigen-specific cytotoxic T cells in healthy donors. Philip, R., Brunette, E., Ashton, J., Alters, S., Gadea, J., Sorich, M., Yau, J., O'Donoghue, G., Lebkowski, J., Okarma, T., Philip, M. Cancer Gene Ther. (1998) [Pubmed]
  21. Grossamide and N-trans-Caffeoyltyramine from Annona crassiflora Seeds. Santos, L.P., Boaventura, M.A., de Oliveira, A.B., Cassady, J.M. Planta Med. (1996) [Pubmed]
  22. Induction of anti-melanoma CTL response using DC transfected with mutated mRNA encoding full-length Melan-A/MART-1 antigen with an A27L amino acid substitution. Abdel-Wahab, Z., Kalady, M.F., Emani, S., Onaitis, M.W., Abdel-Wahab, O.I., Cisco, R., Wheless, L., Cheng, T.Y., Tyler, D.S., Pruitt, S.K. Cell. Immunol. (2003) [Pubmed]
  23. Genetic diversity among clinical and environmental isolates of Aspergillus fumigatus. Debeaupuis, J.P., Sarfati, J., Chazalet, V., Latgé, J.P. Infect. Immun. (1997) [Pubmed]
  24. Fusion transcripts between the HMGIC gene and RTVL-H-related sequences in mesenchymal tumors without cytogenetic aberrations. Kazmierczak, B., Pohnke, Y., Bullerdiek, J. Genomics (1996) [Pubmed]
  25. A superagonist variant of peptide MART1/Melan A27-35 elicits anti-melanoma CD8+ T cells with enhanced functional characteristics: implication for more effective immunotherapy. Rivoltini, L., Squarcina, P., Loftus, D.J., Castelli, C., Tarsini, P., Mazzocchi, A., Rini, F., Viggiano, V., Belli, F., Parmiani, G. Cancer Res. (1999) [Pubmed]
  26. In vitro priming with adenovirus/gp100 antigen-transduced dendritic cells reveals the epitope specificity of HLA-A*0201-restricted CD8+ T cells in patients with melanoma. Linette, G.P., Shankara, S., Longerich, S., Yang, S., Doll, R., Nicolette, C., Preffer, F.I., Roberts, B.L., Haluska, F.G. J. Immunol. (2000) [Pubmed]
  27. Gene Transfer of Tumor-Reactive TCR Confers Both High Avidity and Tumor Reactivity to Nonreactive Peripheral Blood Mononuclear Cells and Tumor-Infiltrating Lymphocytes. Johnson, L.A., Heemskerk, B., Powell, D.J., Cohen, C.J., Morgan, R.A., Dudley, M.E., Robbins, P.F., Rosenberg, S.A. J. Immunol. (2006) [Pubmed]
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